DESCRIPTION: The objective of this project is the understanding of mechanisms involved in DNA damage by ionizing radiation under conditions of direct damage using a combined approach of EPR spectroscopy and strand-break analysis. Experimental studies are planned to investigate the interaction between a range of antitumor drugs and DNA. The investigator proposes to study the following drugs: (a) drugs that covalently bind to DNA such as bleomycin, (b) minor groove binding drugs such as distamycin, and (c) intercalators such as adriamycin. A major aim of this study is to determine to what extent the primary and secondary radicals formed in DNA and drug-DNA systems at 77K, that are detectable by EPR, will lead to strand breaks and relate that to the yields of primary radicals. There are also plans to study the phenomenon of electron migration in DNA using the proposed drugs, and determine the distance the ejected electrons travel, relative to the DNA frame, before being trapped. Briefly, the methodology is to incubate the drugs with aqueous DNA (calf thymus) and then freeze the complex to 77 K. DNA samples will be irradiated with g-rays at 77K and the EPR spectra will be measured at liquid helium temperature and under aerobic and anaerobic conditions. Parallel experiments, under comparable conditions, are also planned to study strand-breaks, using the gel electrophoresis technique and plasmid DNA. The long-range goal of the project is to design molecules (drugs) that can either protect, or sensitize radiation damage to cellular systems, which would be useful in cancer therapy.